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Biomedical subjects

M Muranjan

Publications and source records attributed to M Muranjan.

10 recordsLinked to original sources

Autosomal dominant ectrodactyly with sensorineural deafness.

Ectrodactyly or split hand/split foot malformation as it is now known, is a rare developmental disorder sometimes associated with other systemic malformations. Very few cases of congenital hearing loss coexisting with ectrodactyly have been reported world-wide. We profile one such family with the father and daughter being affected with bilateral foot ectrodactyly minor abnormalities of the 5th fingers and severe sensorineural hearing loss (SNHL). The inheritance in this family was likely to be autosomal dominant. There were no cytogenetically demonstrable structural aberrations in either case.

Adult↗

Receptor protein tyrosine phosphatase alpha activates Src-family kinases and controls integrin-mediated responses in fibroblasts.

BACKGROUND: Fyn and c-Src are two of the most widely expressed Src-family kinases. Both are strongly implicated in the control of cytoskeletal organization and in the generation of integrin-dependent signalling responses in fibroblasts. These proteins are representative of a large family of tyrosine kinases, the activity of which is tightly controlled by inhibitory phosphorylation of a carboxyterminal tyrosine residue (Tyr527 in chicken c-Src); this phosphorylation induces the kinases to form an inactive conformation. Whereas the identity of such inhibitory Tyr527 kinases has been well established, no corresponding phosphatases have been identified that, under physiological conditions, function as positive regulators of c-Src and Fyn in fibroblasts. RESULTS: Receptor protein tyrosine phosphatase alpha (RPTPalpha) was inactivated by homologous recombination. Fibroblasts derived from these RPTPalpha-/- mice had impaired tyrosine kinase activity of both c-Src and Fyn, and this was accompanied by a concomitant increase in c-Src Tyr527 phosphorylation. RPTPalpha-/- fibroblasts also showed a reduction in the rate of spreading on fibronectin substrates, a trait that is a phenocopy of the effect of inactivation of the c-src gene. In response to adhesion on a fibronectin substrate, RPTPalpha-/- fibroblasts also exhibited characteristic deficiencies in integrin-mediated signalling responses, such as decreased tyrosine phosphorylation of the c-Src substrates Fak and p 130(cas), and reduced activation of extracellular signal regulated (Erk) MAP kinases. CONCLUSIONS: These observations demonstrate that RPTPalpha functions as a physiological upstream activator of Src-family kinases in fibroblasts and establish this tyrosine phosphatase as a newly identified regulator of integrin signalling.

Animals↗

Characterization of the human serum trypanosome toxin, haptoglobin-related protein.

Haptoglobin-related protein (HPR) is a serum protein that is >90% homologous to the acute-phase reactant haptoglobin (Hp). Haptoglobin binds and removes free hemoglobin (Hb) from the circulation. Hpr levels are elevated with tumor progression in the serum of some cancer patients, but the relevance of this observation is not understood. HPR is an integral part of two distinct high molecular weight complexes (trypanosome lytic factor 1 (TLF1) and TLF2) that are lytic for the African parasite Trypanosoma brucei brucei. Previous data indicate that HPR represents the toxic component of both trypanosome lytic factors. It has been proposed that after uptake by the parasite, Hb bound to HPR causes lysis in a peroxidase-dependent process. We report that the molecular architecture of HPR in normal human serum is different from that of Hp and that HPR does not bind Hb in normal human serum. Immunodepletion of all detectable Hb from TLF1 does not deplete TLF1 of HPR or trypanolytic activity, suggesting that the mechanism of parasite lysis is Hb-independent.

Animals↗

The trypanocidal Cape buffalo serum protein is xanthine oxidase.

Plasma and serum from Cape buffalo (Syncerus caffer) kill bloodstream stages of all species of African trypanosomes in vitro. The trypanocidal serum component was isolated by sequential chromatography on hydroxylapatite, protein A-G, Mono Q, and Superose 12. The purified trypanocidal protein had a molecular mass of 150 kDa, and activity correlated with the presence of a 146-kDa polypeptide detected upon reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Amino acid sequences of three peptide fragments of the 146-kDa reduced polypeptide, ligand affinity and immunoaffinity chromatography of the native protein, and sensitivity to pharmacological inhibitors, identified the trypanocidal material as xanthine oxidase (EC 1.1.3.22). Trypanocidal activity resulted in the inhibition of trypanosome glycolysis and was due to H2O2 produced during catabolism of extracellular xanthine and hypoxanthine by the purine catabolic enzyme.

Africa↗

Cohen syndrome.

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Abnormalities, Multiple↗

African buffalo serum contains novel trypanocidal protein.

The high ability of African buffalo, as compared to domestic cattle, to control infections with Trypanosoma brucei brucei ILTat 1.4 organisms did not correlate with the timing or magnitude of parasite surface coat-specific antibody responses and may have resulted from the constitutive presence in buffalo blood of a novel trypanocidal factor. Buffalo plasma and serum contained material that killed bloodstream stage T. b. brucei, T. b. rhodesiense, T. b. gambiense, T. evansi, T. congolense, and T. vivax organisms during four h of incubation at 37 degrees C in vitro. Serum from eland was also trypanocidal whereas serum from oryx, waterbuck, yellow-back duiker, cattle, horse, sheep, goat, mouse, rat, and rabbit was not trypanocidal. The buffalo serum trypanocidal material was not lipoprotein, or IgG, and had the following properties: 1) a density of > 1.24 g/ml determined by flotation ultracentrifugation; 2) insolubility in 50% saturated ammonium sulphate; 3) non-reactivity with anti-bovine IgM, and anti-bovine IgG; 4) non-reactivity with protein G, and protein A; 5) a relative molecular mass of 152 kDa determined by chromatography on Sephacryl S 300, and of 133 kDa determined by chromatography of the 50% SAS cut of IgG-depleted buffalo serum on Superose 12; 6) no associated cholesterol; and 7) inactivation by digestion with proteinase K that was immobilized on agarose.

Animals↗

Intestinal giardiasis: an unusual cause for hypoproteinemia.

Malabsorption is a well-known complication of infection with Giardia lamblia. However, selective protein-losing enteropathy is rare. We report a child with anasarca due to hypoalbuminemia as a result of gastrointestinal protein loss. Investigations established giardiasis as the etiology. The child returned to normal health after treatment with metronidazole.

Anti-Infective Agents↗